CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials

Chintala, Navin K.; Restle, David; Quach, Hue Tu; Saini, Jasmeen; Bellis, Rebecca; Offin, Michael; Beattie, Jason; Adusumilli, Prasad S.

doi:10.1016/j.lungcan.2021.05.004

Cited by 19 publications

(10 citation statements)

References 110 publications

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“…A phase II trial with 24 included patients was concluded in May 2020 and compared oncolytic vaccine treatment ONCOS-102 and standard treatment with pemetrexed/cisplatin. The results of this trial are still pending [50].…”

Section: Therapeutic Cancer Vaccines In Mesotheliomamentioning

confidence: 96%

Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Štrbac

Dolžan

2022

IJMS

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Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy improved the overall survival. However, the regimen of pemetrexed/cisplatin doublet has not been changed as a standard treatment since 2004. Novel combinations of ipilimumab and nivolumab have only been approved for clinical use in late 2020. The aim of this review was to systematically summarize findings on novel treatment options in mesothelioma. We searched available medical databases online, such as PubMed and Clinicaltrials.gov, to systematically review the literature on novel approaches in immunotherapy, vaccines, and Chimeric Antigen Receptor (CAR)-T cell therapy in mesothelioma. We manually screened 1127 articles on PubMed and 450 trials on ClinicalTrials.gov, and 24 papers and 12 clinical trials published in the last ten years were included in this review. Immunotherapy that was swiftly introduced to treat other thoracic malignancies was slow to reach desirable survival endpoints in mesothelioma, possibly due to limited patient numbers. Novel treatment approaches, such as CAR-T cell therapy, are being investigated. As the incidence of mesothelioma is still rising globally, novel treatment options based on a better understanding of the tumor microenvironment and the genetic drivers that modulate it are needed to support future precision-based therapies.

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Section: Therapeutic Cancer Vaccines In Mesotheliomamentioning

confidence: 96%

Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Štrbac

Dolžan

2022

IJMS

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“…Using this strategy, genetically engineered T-cells are administrated against a specific tumour-associated antigen such as mesothelin. This strategy has been investigated in several phase I studies, mainly in combination therapies such as ICI [ 105 , 106 ].…”

Section: Mesotheliomamentioning

confidence: 99%

Rare thoracic cancers: a comprehensive overview of diagnosis and management of small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours

et al. 2023

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Despite the progress in outcomes seen with immunotherapy in various malignancies, including nonsmall cell lung cancer, the benefits are less in small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours. New effective treatment options are needed, guidedviamore in-depth insights into the pathophysiology of these rare malignancies. This review comprehensively presents an overview of the clinical presentation, diagnostic tools, staging systems, pathophysiology and treatment options for these rare thoracic cancers. In addition, opportunities for further improvement of therapies are discussed.

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“…Bispecific CAR-T cells are designed by engineering a single CAR molecule with two or more distinct binding domains. Multi-target CAR-T cell therapies are produced by mixing different CAR-T cell products targeting single antigens before infusion or transducing T cells with multiple CAR constructs CAR-T cells expressing bispecific T cell engagers (BiTEs) recruit bystander T cells against a second TAA [94] . The synNotch CAR-T cells offer benefits beyond enhanced tumor specificity by preventing premature T cell differentiation and exhaustion, further enabling T cells to maintain a long-lived memory [45,85] .…”

Section: Novel Car Strategiesmentioning

confidence: 99%

Overcoming tumor antigen heterogeneity in CAR-T cell therapy for malignant mesothelioma (MM)

D’Souza¹,

Dimou²,

Bughda³

et al. 2022

J Cancer Metastasis Treat

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Malignant mesothelioma (MM) is a rare, aggressive solid tumor with limited therapeutic options and poor therapeutic response. The role of immunotherapy in MM is now well established and therapeutic options, such as checkpoint inhibitors, are increasingly being approved. Chimeric antigen receptor (CAR)-T cell therapy is successfully implemented in several hematologic cancers, but currently has inadequate effect in solid tumors, owing to several limitations, such as trafficking and infiltration, limited T cell persistence and exhaustion, the immunosuppressive TME and tumor antigen heterogeneity. The lack of uniform and universal expression of tumor-associated antigens (TAAs) on tumor cells, as well as TAA heterogeneity following tumor editing post-therapy, are issues of significant importance to CAR-T cell and associated antigen-targeting therapies. Our review discusses the concept of tumor antigen heterogeneity in MM, the consequences for CAR-T cell therapies and the strategies to overcome it.

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CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials

Cited by 19 publications

References 110 publications

Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Rare thoracic cancers: a comprehensive overview of diagnosis and management of small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours

Overcoming tumor antigen heterogeneity in CAR-T cell therapy for malignant mesothelioma (MM)

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